Diabetes, Type I

Diabetes mellitus type 1 – also known as type 1 diabetes, T1DM, formerly insulin dependent or juvenile diabetes – is an autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body disorder associated with the destruction of insulin-producing beta cells of the pancreas.

Several emerging lines of evidence suggest that type I diabetes may be caused by microbes. This evidence includes the presence of a diabetes microbiome as well as the presence of autoantibodies, which are themselves associated with persistent infection.

Evidence for infectious cause

The advent of culture-independent approaches for detecting the presence of microbes has given increasing evidence of the possible role of microbes in type I diabetes. For example, a 2012 paper correlated hemoglobin A1c (HbA1c) levels, an indicator of a hyperglycaemic state, on C. pneumoniae infection and disease chronicity.1) Using Real Time-Polymerase Chain Reaction (RT-PCR), C. pneumoniae DNA was detected in 46.5% of the patients with T1DM compared to 10.5% of non-diabetic paediatric controls. Further, IgG/IgA C. pneumoniae antibody positivity was significantly more common in patients in poor metabolic control (HbA1c > 9%) versus patients in good metabolic control (HbA1c < 7%).

Successive infection

A 2010 Norwegian paper showed that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection, characterized by the presence of viral RNA in blood.2)

Intestinal microbiome

Growing evidence suggests a role for intestinal microbiome alterations in autoimmune disease development, including type 1 diabetes.3) In a 2011 paper, Giongo et al. collected stool samples at three points each from eight Finnish children. Four of the children remained clinically healthy throughout the study, and four were diagnosed with type I diabetes at or near the time of the third sampling.4) As the diabetic children’s disease progressed, so did the irregular makeup of their gut bacteria. The researchers concluded that level of bacterial diversity diminishes over time in these autoimmune subjects relative to that of age-matched nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases over time.

Also, patients with type I diabetes have increased small intestinal permeability compared to controls.5) Such higher permeability would allow microbes easier access to the remainder of the body.


Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. 6)

As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. In diabetes, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. Glycated hemoglobin (wikipedia)

The overall quality score of clinical practice guidelines ranges between 3 and 6.25. While NICE's guidelines scored the highest, the guidelines of the National Diabetes Foundation scored the lowest. 7)

18β-GA provides a potential implication to diabetes mellitus and its complications. 8)

Hyperuricaemia was associated with an unfavourable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients. 9)

Animal models

Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model.10) The incidence of diabetes can be reduced in diabetes-prone rats by preventing an increase in small intestine epithelial permeability.11)


Due to its high toxicity to beta cells, the microbial byproduct streptozotocin has also been long used for inducing insulitis and diabetes on experimental animals. Streptozotocin was originally identified in the late 1950s as an antibiotic.12) The drug was discovered in a strain of the soil microbe Streptomyces achromogenes by scientists at the drug company Upjohn (now part of Pfizer) in Kalamazoo, Michigan. The soil sample in which the microbe turned up had been taken from Blue Rapids, Kansas, which can therefore be considered the birthplace of streptozotocin. Upjohn filed for patent protection for the drug in August 1958 and U.S. Patent 3,027,300 was granted in March 1962.

In the mid-1960s streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that normally regulate blood glucose levels by producing the hormone insulin. This suggested the drug's use as an animal model of diabetes,13) 14) and as a medical treatment for cancers of the beta cells.15) In the 1960s and 1970s the National Cancer Institute investigated streptozotocin's use in cancer chemotherapy. Upjohn filed for FDA approval of streptozotocin as a treatment for pancreatic islet cell cancer in November 1976, and approval was granted in July 1982. The drug was subsequently marketed as Zanosar. Streptozotocin is now marketed by the generic drug company Sicor (Teva).

Lammi et al. have hypothesized that Streptomyces produce another toxin, bafilomycin A1, that could be the cause of pancreatic beta-cell damage.16)


Autoimmune diseases such as type I diabetes are characterized largely by the presence of autoantibodies. While autoantibodies were reported over a century ago, many scientists at the time were unwilling to accept the possibility that the immune system attacks its own cells. Ehrlich argued that autoimmunity was not possible and proposed the theory of horror autotoxicus to describe the body's innate aversion to immunological self-destruction by the production of autoantibodies.

Now that humans are understood to be the product of multiple genomes, increasing evidence supports Ehrlich's view. When an innate immune system is forced to respond to a chronic microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms., the resulting cascade of chemokines and cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. will also stimulate an adaptive response. Antibodies are notoriously polyspecific, and the likelihood that antibodies generated to target metagenomic fragments will also target human proteins (target “self”) is finite.

A litany of research implies a re-evaluation of the “autoantibody.” Recently researchers have shown that certain autoantibodies are created in response to several well-studied pathogens and in a variety of states.

Read more

===== Notes and comments =====

We have a T1 Diabetic in our Porto data: https://mpkb.org/_detail/home/publications/perezimprovements.gif?id=home%3Apublications%3Aperez_congress_on_autoimmunity_2008

Trevor's comment to me about T1D:

Pay attention to last bit of hans cleaver's talk he finishes by talking about how the vdrThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. can allow pancreatic tissue which has been damaged by surgery, to recreate itself there's a lot of talk about how it's impossible; certainly based on cleaver's work, this doesn't seem to be the case 4-5 years ago: Trevor saw video of pancreas being surrounded by macrophages we have one person (debbie y) on the MP with t1d; her insulin requirements have been dropping and it's pulsing in line with Z; there is a response; https://www.marshallprotocol.com/view_topic.php?id=8020&forum_id=35&jump_to=197496#p197496

Search the alumni forums for people with these indications early signs of response 10-day cycle of insulin response slow drop in insulin demand

===== References =====

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Stene LC, Oikarinen S, Hyöty H, Barriga KJ, Norris JM, Klingensmith G, Hutton JC, Erlich HA, Eisenbarth GS, Rewers M. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes. 2010 Dec;59(12):3174-80. doi: 10.2337/db10-0866. Epub 2010 Sep 21.
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